Physical disability and poor health often accompany knee osteoarthritis (OA, joint pains), particularly as people age. This decline in function and quality of life is a complex phenomenon associated with numerous factors including pain, poor physical fitness, obesity, co-morbidity, low self-efficacy and lower extremity impairments. In addition to the functional losses associated with knee OA (joint pain) and aging, low levels of daily physical activity and exercise are common problems in this population for whom arthritis (joint pains) is a major reason for activity limitation. Osteoarthritis is the most common type of arthritis, affecting 20 million people in America alone (Daniel O et al: 2006).
Community survey data in rural and urban areas of India shows the prevalence of osteoarthritis to be in the range of 17-60.6% (M K Sharma et al; 2007).
Osteoarthritis (OA), also known as degenerative arthritis or degenerative joint disease, is a clinical syndrome in which low-grade inflammation results in pain in the joints, caused by abnormal wearing of the cartilage that covers and acts as a cushion inside joints and destruction or decrease of synovial fluid that lubricates those joints. As the bone surfaces become less protected by cartilage, the patient experiences pain upon weight bearing, including walking and standing. Due to decreased movement because of the pain, regional muscles may atrophy, and ligaments may become more lax. OA is the most common form of arthritis (Conaghan et al., 2008), and the leading cause of chronic disability in the United States, MMWR Morb Morta, 2008.
OA affects nearly 21 million people in the United States, accounting for 25% of visits to primary care physicians, and half of all NSAID (Nonsteroidal Anti-Inflammatory Drugs) prescriptions. It is estimated that 80% of the population will have radiographic evidence of OA by age 65, although only 60% of those will be symptomatic. (Green G A (2001). “Understanding NSAIDs: from aspirin to COX-2”. Clin Cornerstone 3 (5): 50-60. PMID 11464731) In the United States, hospitalizations for osteoarthritis soared from about 322,000 in 1993 to 735,000 in 2006. (Hospitalizations for Osteoarthritis Rising Sharply Newswise, Retrieved on Sep. 4, 2008.)
Symptoms of OA: Joint pain, morning stiffness lasting less than 30 minutes, joint instability or buckling, loss of function.
Signs of OA: Bony enlargement at affected joints, limitation of range of motion crepitus on motion, pain with motion, malalignment and/or joint deformity.
Current Management
Current treatment for OA is relatively limited. As there are currently no pharmacological agents capable of retarding or preventing the disease. Treatment is predominantly focused on relief of pain, and maintenance of quality of life and functional independence.
Aside from weight reduction and avoiding activities that, exert excessive stress on the joint cartilage, there is no specific treatment to halt cartilage degeneration or to repair damaged cartilage in osteoarthritis. The goal of treatment in osteoarthritis is to reduce joint pain and inflammation while improving and maintaining joint function.
The first line of drug treatment is with analgesics and non-steroidal anti-inflammatory drugs (NSAIDS). Only a few of these NSAIDS are readily available as OTC products from pharmacies without prescription as potential treatments for the pain and for other pain-syndromes. Standard references to the therapy of painful inflammatory disease attest to both the efficacy and adverse effects of these particular NSAIDs.
Pharmacological Therapy
1. Analgesic Agents
Several studies have shown acetaminophen to be superior to placebo and equivalent to non steroidal anti-inflammatory agents (NSAIDs) for the short-term management of OA pain. At present acetaminophen (up to 4,000 mg/daily) is the recommended initial analgesic of choice for symptomatic OA. However, many patients eventually require NSAIDs or more potent analgesics to control pain. Oral glucosamine and chondroitin sulfate have been shown (each individually) to have a mild to moderate analgesic, effect in several double-blind, placebo-controlled studies.
2. COX-2 Inhibitors
Cyclooxygenase-2 (COX-2) inhibitors are a class of non steroidal anti-inflammatory agents (NSAIDs) that received Food and Drug Administration (FDA) approval. These specific COX-2 inhibitors appear to be as effective as current non-selective NSAIDs in treating the pain and inflammation of arthritis. Their theoretical advantage, however, is that they will cause significantly less toxicity than conventional NSAIDs, particularly in the GI tract. Non steroidal anti-inflammatory drags (NSAIDs) exert their anti-inflammatory effect primarily by inhibiting an enzyme called cyclooxygenase (COX), also known as prostaglandin (PG) synthase. COX catalyzes the conversion of the substrate molecule, arachidonic acid, to prostanoids. Prostanoids consist of prostaglandins E, D and F2α, prostacyclin and thromboxane. The major inflammatory vasoactive prostanoids are PGE2α and prostacyclin. Thromboxane is critical for platelet clotting, while PGD2 is involved in allergic reactions and PGF2α in uterine contraction.
In addition to their inflammatory potential, prostaglandins also contribute to important homeostatic functions, such as maintenance of the gastric lining, renal blood flow, and platelet aggregation. Reduction of prostaglandin levels in these organs can result in the well-recognized side effects of traditional non-selective NSAIDs—that is, gastric ulceration, renal insufficiency, and prolonged bleeding time. The elderly are at higher risk for these side effects. For example, adults over the age of 60 who are taking NSAIDs have a 4-5 fold higher risk of gastrointestinal bleeding or ulceration then their age-matched counterparts. Other risk factors for NSAID-induced GI bleed include prior peptic ulcer disease and concomitant steroid use. Potential renal toxicities of NSAIDs include azotemia, proteinura, and renal failure requiring hospitalization. Hematologic and cognitive abnormalities nave also been reported with several NSAIDs. Therefore, in elderly patients, and those with a documented history of NSAID-induced ulcers, traditional non-selective NSAIDs should be used with caution, usually in lower dose and in conjunction with a proton pump inhibitor. Renal function should be monitored in the elderly.
3. Local Analgesic Agents
Local analgesic therapies include topical capsaicin and methyl salicylate creams. Occasionally in late stage disease, patients will require narcotic, analgesics to control pain.
4. Intra Articular Therapies
Judicious use of intra-articular glucocorticoid injections is appropriate for OA patients who cannot tolerate, or whose pain is not well controlled by, oral analgesic and anti-inflammatory agents. Periarticular injections may effectively treat bursitis or tendonitis that can accompany OA. The need for four or more intra-articular injections suggests the need for orthopedic intervention. Intraarticular injection of hyaluronate preparations has been demonstrated in several small clinical trials to reduce pain in OA of the knee. These injections are given in a series of 3 or 5 weekly injections (depending on the specific preparation) and may reduce pain for up to 6 months in some patients.
Non-pharmacological Management includes Weight reduction. Exercise/resistive strengthening.
Side Effects of Current Therapies
Analgesics: These agents are not recommended for prolonged use because they cause constipation and increase the risk of felling, particularly in the elderly.
NSAID: The most common side effects are dyspepsia, diarrhea, abdominal pain, gastric ulceration, renal insufficiency, and prolonged bleeding time.